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It's been years since I started taking metformin for diabetes, and lots of new medicines have come out since then. Should I talk to my doctor about switching to a newer drug? Are the newer ones better?

— Anonymous

The short answer is no. If your sugar level is controlled and you have a hemoglobin A1C level below 7 percent, there is no need to add or switch medications. If your sugar level is not controlled, however, and you are taking the maximum amount of metformin, another medicine is required to control it better. This usually means adding a medication rather than switching drugs completely. A class of drugs called insulin secretagogues (drugs that stimulate insulin secretion in the pancreas) — such as glyburide, glipizide, and glimepiride — can be used as additional medicines. There has been some controversy over the use of newer diabetes medicines, especially after a recent study indicated that rosiglitazone (Avandia, a relatively new medicine) could have some heart-related side effects.

The ultimate goal of treating diabetes is to prevent premature death from its complications. However, no study has ever demonstrated that any of the medicines currently on the market reduce the chance of early death.

Having said this, we know that by maintaining normal glucose levels we can reduce diabetes complications such as eye disease (including blindness) and kidney failure. This in turn improves the quality of life of those who suffer from diabetes. Also, our hope is that better control of glucose will prevent cardiac complications and strokes. In fact, a study is currently underway to determine whether achieving a normal glucose level prevents heart attacks, strokes, and premature death.

Because diabetes is a progressive illness, almost all diabetics will eventually require more than one medicine to control their glucose. About 75 percent of diabetics will require more than one medicine to control their glucose nine years after diagnosis. A large number of people require at least three medicines, a combination of insulin and oral medicines, or insulin alone.

Diabetes is a complex disease. Treatment with a combination of short- and long-acting medicines, secretagogues, and insulin sensitizers such as metformin, rosiglitazone, and pioglitazone is usually necessary. We gauge the adequacy of the medicines' control of sugar by measuring the variations in glucose values and hemoglobin A1C.

Diabetes is usually a progressive disease in which about 10 percent of the pancreatic cells that produce insulin stop functioning every year. This is a rough estimate. In a large study in England, the average person with type 2 diabetes required insulin administration six years after diagnosis. However, we can delay the progression by achieving good glucose control and protecting the ability of the pancreatic cells that produce insulin. Some medicines are better at preserving the function of these beta cells than others.

To achieve good control, physicians use all the available medicines as needed.

There is a sequential use of medicines that makes sense for patients based on what we know about their particular cases. For most diabetics, the first medicine used is metformin or a secretagogue such as glyburide or glipizide. The newest addition in this class is glimepiride, which is similarly effective but more expensive.

For diabetics who are also obese, starting with metformin makes sense because this drug addresses insulin resistance — the central problem for many obese diabetics — and is associated with weight loss, or at least less weight gain than other drugs.

If glucose levels are not controlled with the above medicines, or combinations thereof, thiazolinediones such as pioglitazone (Actos) and rosiglitazone (Avandia) can be considered. If sugar levels after your meals are high, then short-acting secretagogues such as repaglinide and nateglinide, or other newer medicines such as sitagliptin (Januvia) and exenatide (Byetta), can also be considered.

In current practice, insulin is prescribed if blood sugar control remains poor despite the use of a combination of various oral medicines. It is increasingly common, however, to prescribe insulin early in the disease process to achieve better control of sugar and prevent the decline of the insulin-producing cells. Stay tuned for more developments in this area.

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